Variant 4-3518035-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002337.4(LRPAP1):c.750T>C(p.Ala250Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,601,412 control chromosomes in the GnomAD database, including 19,842 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.15 ( 1808 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18034 hom. )

Consequence

LRPAP1
NM_002337.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00001405

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.34

Variant links:

Genes affected

LRPAP1 (HGNC:6701): (LDL receptor related protein associated protein 1) This gene encodes a protein that interacts with the low density lipoprotein (LDL) receptor-related protein and facilitates its proper folding and localization by preventing the binding of ligands. Mutations in this gene have been identified in individuals with myopia 23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

LRPAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 4-3518035-A-G is Benign according to our data. Variant chr4-3518035-A-G is described in ClinVar as [Benign]. Clinvar id is 3059677.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-3518035-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRPAP1	NM_002337.4 link	c.750T>C	p.Ala250Ala	splice_region_variant, synonymous_variant	5/8	ENST00000650182.1	NP_002328.1	P30533
LRPAP1	NR_110005.2 link	n.713T>C		splice_region_variant, non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182.1 link	c.750T>C	p.Ala250Ala	splice_region_variant, synonymous_variant	5/8		NM_002337.4	ENSP00000497444.1		P30533

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22487

AN:

152016

Hom.:

1806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0831

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.130

AC:

31428

AN:

242158

Hom.:

2444

AF XY:

0.130

AC XY:

17184

AN XY:

131828

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0958

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.000662

Gnomad SAS exome

AF:

0.0861

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.152

AC:

220728

AN:

1449280

Hom.:

18034

Cov.:

AF XY:

0.151

AC XY:

108393

AN XY:

719852

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.000380

Gnomad4 SAS exome

AF:

0.0866

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.148

AC:

22512

AN:

152132

Hom.:

1808

Cov.:

AF XY:

0.143

AC XY:

10653

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.0836

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.155

Hom.:

624

Bravo

AF:

0.153

Asia WGS

AF:

0.0470

AC:

165

AN:

3478

EpiCase

AF:

0.175

EpiControl

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LRPAP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.034

DANN

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over